■内脏利什曼病(VL)是一种重要的热带和被忽视的疾病,是一个严重的全球健康问题。吞噬细胞和寄生虫之间的初始相互作用对于确定病原体启动感染的能力至关重要,并形成随后的免疫反应。而1型T细胞诱导IL-6,IL-1β,TNF-α,和单核细胞/巨噬细胞产生IL-12来对抗感染,2型T细胞与调节表型(IL-10和TGF-β)和成功的感染建立相关。最近,我们小组证明了重要的Th1/Th17T细胞群的作用,粘膜相关不变T(MAIT)细胞,在VL。MAIT细胞可以通过在MR1依赖性激活后产生TNF-α和IFN-γ来响应婴儿乳球菌。
■这里,我们描述了MR1阻断婴儿乳球菌内化对循环中性粒细胞和单核细胞功能特征的影响,以及MR1阻断对体外全血培养物可溶性介质特征的影响.
■总的来说,我们的数据显示,与无症状和未感染的对照组相比,VL患者的活化中性粒细胞百分比更高.此外,MR1阻断导致来自无症状个体的非活化中性粒细胞的TNF-α和TGF-β产生降低。此外,VL患者单核细胞产生的TNF-α和IL-10较高。在体外产生的可溶性介质的分析中,MR1阻断诱导AS组细胞培养物中IFN-γ的减少和IL-10、IL-27和IL-33的增加,与2型有害反应相关的细胞因子模式。
■这些数据证实了以下假设:MR1限制性反应与利什曼原虫感染期间的保护作用有关。
UNASSIGNED: Visceral leishmaniasis (VL) is an important tropical and neglected disease and represents a serious global health problem. The initial interaction between the
phagocytes and the parasite is crucial to determine the pathogen\'s capacity to initiate infection and it shapes the subsequent immune response that will develop. While type-1 T-cells induce IL-6, IL-1β, TNF-α, and IL-12 production by monocytes/macrophages to fight the infection, type-2 T-cells are associated with a regulatory phenotype (IL-10 and TGF-β) and successful infection establishment. Recently, our group demonstrated the role of an important Th1/Th17 T-cell population, the mucosal-associated invariant T (MAIT) cells, in VL. MAIT cells can respond to L. infantum by producing TNF-α and IFN-γ upon MR1-dependent activation.
UNASSIGNED: Here, we describe the impact of the MR1-blockage on L. infantum internalization on the functional profile of circulating neutrophils and monocytes as well as the impact of the MR1-blockage on the soluble mediator signatures of in vitro whole blood cultures.
UNASSIGNED: Overall, our data showed that VL patients presents higher percentage of activated neutrophils than asymptomatic and non-infected controls. In addition, MR1 blockade led to lower TNF-α and TGF-β production by non-activated neutrophils from asymptomatic individuals. Moreover, TNF-α and IL-10 production by monocytes was higher in VL patients. In the analysis of soluble mediators produced in vitro, MR1-blockade induced a decrease of IFN-γ and an increase of IL-10, IL-27 and IL-33 in the cell cultures of AS group, a cytokine pattern associated with type 2 deleterious response.
UNASSIGNED: These data corroborate the hypothesis that MR1-restricted responses are associated to a protective role during Leishmania infection.